Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity.
Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress....
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Public Library of Science (PLoS)
2010
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oai:doaj.org-article:52aa547cdf234f33a0cd08927f35c3f22021-11-18T06:01:47ZTransduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity.1553-73661553-737410.1371/journal.ppat.1001018https://doaj.org/article/52aa547cdf234f33a0cd08927f35c3f22010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20686664/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress. Here we report the identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073-1081-reactive CTL clone isolated from a patient with chronic HCV infection. We characterized this HCV TCR by expressing it in human T cells and analyzed the function of the resulting HCV TCR-transduced cells. Our results indicate that both the HCV TCR-transduced CD4(+) and CD8(+) T cells recognized the HCV NS3:1073-1081 peptide-loaded targets and HCV(+) hepatocellular carcinoma cells (HCC) in a polyfunctional manner with cytokine (IFN-gamma, IL-2, and TNF-alpha) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-) Jurkat cells and CD4(+) PBL-derived T cells indicated this TCR was CD8-independent, a property consistent with other high affinity TCRs. HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections.Yi ZhangYeuying LiuKelly M MoxleyLucy Golden-MasonLucy Golden-MasonMichael G HughesTongxin LiuMirjam H M HeemskerkHugo R RosenMichael I NishimuraPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 7, p e1001018 (2010) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Yi Zhang Yeuying Liu Kelly M Moxley Lucy Golden-Mason Lucy Golden-Mason Michael G Hughes Tongxin Liu Mirjam H M Heemskerk Hugo R Rosen Michael I Nishimura Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| description |
Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress. Here we report the identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073-1081-reactive CTL clone isolated from a patient with chronic HCV infection. We characterized this HCV TCR by expressing it in human T cells and analyzed the function of the resulting HCV TCR-transduced cells. Our results indicate that both the HCV TCR-transduced CD4(+) and CD8(+) T cells recognized the HCV NS3:1073-1081 peptide-loaded targets and HCV(+) hepatocellular carcinoma cells (HCC) in a polyfunctional manner with cytokine (IFN-gamma, IL-2, and TNF-alpha) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-) Jurkat cells and CD4(+) PBL-derived T cells indicated this TCR was CD8-independent, a property consistent with other high affinity TCRs. HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections. |
| format |
article |
| author |
Yi Zhang Yeuying Liu Kelly M Moxley Lucy Golden-Mason Lucy Golden-Mason Michael G Hughes Tongxin Liu Mirjam H M Heemskerk Hugo R Rosen Michael I Nishimura |
| author_facet |
Yi Zhang Yeuying Liu Kelly M Moxley Lucy Golden-Mason Lucy Golden-Mason Michael G Hughes Tongxin Liu Mirjam H M Heemskerk Hugo R Rosen Michael I Nishimura |
| author_sort |
Yi Zhang |
| title |
Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_short |
Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_full |
Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_fullStr |
Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_full_unstemmed |
Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity. |
| title_sort |
transduction of human t cells with a novel t-cell receptor confers anti-hcv reactivity. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/52aa547cdf234f33a0cd08927f35c3f2 |
| work_keys_str_mv |
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| _version_ |
1718424664863145984 |